The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines.
The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines.
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DOI：
10.3389/fcell.2021.789427
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发表时间：
2021
影响因子：
5.5
通讯作者：
Yu YT
中科院分区：
文献类型：
--
作者：
Morais P;Adachi H;Yu YT
目前的COVID-19大流行是全球混乱的一个巨大来源，迄今已导致全球2.5亿例COVID-19病例和近500万人死亡。人们从一开始就认识到，只有有效的疫苗才能摆脱大流行，因此，在病毒序列数据的可用性推动下，COVID-19疫苗的竞争立即开始。辉瑞- biontech和Moderna Therapeutics于2020年开发了两种基于mRNA技术的新型疫苗平台（分别为comirnaty®和spikevax®），是第一批疗效超过90%的疫苗平台。两者均由n1 -甲基伪尿嘧啶修饰的编码SARS-COVID-19刺突蛋白的mRNA组成，并通过脂质纳米颗粒（LNP）制剂递送。由于核糖核酸的递送问题几十年前就已为人所知，LNPs的成功很快被许多人誉为COVID-19 mRNA疫苗的无名英雄。然而，Curevac mRNA疫苗（CVnCoV）的临床试验疗效结果表明，递送系统并不是成功的唯一关键。CVnCoV由未修饰的mRNA组成（编码与Moderna和辉瑞- biontech的mRNA疫苗相同的刺突蛋白），并与辉瑞- biontech的疫苗（Acuitas ALC-0315）使用相同的LNP配制。然而，它的功效只有48%。这种显著的疗效差异可能归因于辉瑞- biontech和Moderna的mRNA疫苗中存在一种关键的RNA修饰（n1 -甲基假尿嘧啶）（但在CVnCoV中没有）。本文重点介绍了n1 -甲基假尿嘧啶的特点及其对mRNA疫苗的贡献。
The current COVID-19 pandemic is a massive source of global disruption, having led so far to two hundred and fifty million COVID-19 cases and almost five million deaths worldwide. It was recognized in the beginning that only an effective vaccine could lead to a way out of the pandemic, and therefore the race for the COVID-19 vaccine started immediately, boosted by the availability of the viral sequence data. Two novel vaccine platforms, based on mRNA technology, were developed in 2020 by Pfizer-BioNTech and Moderna Therapeutics (comirnaty® and spikevax®, respectively), and were the first ones presenting efficacies higher than 90%. Both consisted of N1-methyl-pseudouridine-modified mRNA encoding the SARS-COVID-19 Spike protein and were delivered with a lipid nanoparticle (LNP) formulation. Because the delivery problem of ribonucleic acids had been known for decades, the success of LNPs was quickly hailed by many as the unsung hero of COVID-19 mRNA vaccines. However, the clinical trial efficacy results of the Curevac mRNA vaccine (CVnCoV) suggested that the delivery system was not the only key to the success. CVnCoV consisted of an unmodified mRNA (encoding the same spike protein as Moderna and Pfizer-BioNTech’s mRNA vaccines) and was formulated with the same LNP as Pfizer-BioNTech’s vaccine (Acuitas ALC-0315). However, its efficacy was only 48%. This striking difference in efficacy could be attributed to the presence of a critical RNA modification (N1-methyl-pseudouridine) in the Pfizer-BioNTech and Moderna’s mRNA vaccines (but not in CVnCoV). Here we highlight the features of N1-methyl-pseudouridine and its contributions to mRNA vaccines.
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影响因子：
64.8
作者：
Fernandez, Israel S.;Chyan Leong Ng;Kelley, Ann C.;Wu, Guowei;Yu, Yi-Tao;Ramakrishnan, V.
通讯作者：
Ramakrishnan, V.
影响因子：
7.8
作者：
Buschmann MD;Carrasco MJ;Alishetty S;Paige M;Alameh MG;Weissman D
通讯作者：
Weissman D
影响因子：
4.7
作者：
Adachi H;Hengesbach M;Yu YT;Morais P
通讯作者：
Morais P
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
5.4
作者：
Alfagih IM;Aldosari B;AlQuadeib B;Almurshedi A;Alfagih MM
通讯作者：
Alfagih MM